NIH DRUG DISCOVERY AND DEVELOPMENT CONSULTING SERVICES STATEMENT OF WORK Background The National Institutes of Health (NIH) is the nation?s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people?s health and save lives. The National Institute of Neurological Disorders and Stroke (NINDS) is a part of the National Institutes of Health (NIH), conducting research into the causes, treatment, and prevention of neurological disorders and stroke. The NINDS mission is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NIH Blueprint for Neuroscience (BPN) Research is a consortium of 15 NIH Institutes and Centers that support neuroscience research, established the Neurotherapeutics Network as a pipeline between the typical endpoint of NIH-funded research and the beginning of industry drug development. The BPN provides neuroscience researchers with funding and access to a full range of industry-style drug development services and expertise. The program is intended for projects requiring medicinal chemistry optimization and CRO support through phase I clinical testing. Each project is directed by a Lead Development Team composed of the principal investigator, industry consultants hired by NIH, and NIH staff. This team maps out a research strategy, including milestones, and oversees implementation by contract research providers. Bioactivity and efficacy studies are funded through an award to the principal investigator; other research services are provided without cost to the PI through NIH contracts. STATEMENT OF OBJECTIVE The NIH is seeking senior-level, industry-experienced drug discovery and development consultants with expertise in the following specific disciplines to provide leadership and technical guidance on drug discovery and development projects in the Blueprint Neurotherapeutics Network and possibly other NIH neuroscience-focused drug discovery and development programs. ? Chemical Manufacturing and Controls (CMC/Pharmaceutics) ? Process Chemistry ? Medicinal Chemistry ? Regulatory Affairs ? Bioactivity Assay Development ? Toxicology ? Drug Metabolism and Pharmacokinetics ? Phase I Clinical Consultant SCOPE OF WORK Each consulting contract will be specific to one or more areas of expertise as outlined in this Statement of Work, and will reflect the NIH time commitment needs for the specific areas of expertise. Consultants hired under this requirement will not only make significant contributions to promising drug discovery projects that have been selected through a rigorous peer-review process, they will also help shape an innovative, high-profile program that may serve as a model for future NIH drug discovery efforts. Contract consultants will be expected to provide feedback and guidance on projects to the NIH and to Blueprint Lead Development Team (LDT) members through conference calls and by email. Consultants may serve on an ad hoc basis or as members of LDTs. Consultants will be expected to offer input on project milestones, development strategy, study design, and data interpretation. Specific consulting responsibilities will depend on the expertise of the individual consultant and the needs of individual projects. The BPN currently has projects in the exploratory through lead-optimization stages. Some projects will proceed to the candidate selection, IND, and clinical trial stages. Project continuation will depend on the achievement of project-specific milestones and portfolio management. Since 2011, fifteen projects have entered the BPN, and seven have been discontinued based on milestone evaluations. General Requirements Consultants may serve on Blueprint Lead Development Teams (LDTs), which require a regular time commitment of 3-10 hours per week, including meeting and preparation time. Each LDT meets for approximately 2 hours every 1-2 weeks by teleconference. Consultants may be asked to serve as co-chairs of LDTs. A consultant serving as an LDT co-chair shall facilitate LDT discussions, work with an NIH project manager by email and telephone to maintain and communicate the overall project strategy to other LDT members, and advise the principal investigator on the preparation of milestone reports. Co-chairs for LDTs are selected based on breadth of expertise and previous experience serving in a comparable role. A teleconference call with all consultants is held twice per month to discuss programmatic issues of broad interest. Specific Discipline Requirements 1. Chemical Manufacturing and Controls (CMC/Pharmaceutics) Consultants will serve as a resource to LDT members for the regulatory requirements, processes, and logistics to conduct drug development activities for small molecule compounds from the preclinical stage through to the initial clinical stage. Consultants may be asked to provide strategic guidance for CMC regulatory activities necessary to enable preclinical drug product manufacturing, IND enabling studies, and clinical trials. The role of the CMC consultant may include but is not limited to the following responsibilities and tasks: ? Lead CMC activities for compounds in development, in accordance with the US regulatory and the ICH guidelines. ? Provide expertise in drug substance manufacturing, analytical method development, and process development for small molecules. ? Provide pharmaceutical sciences leadership in chemical manufacturing, formulation, and product development for small molecules. ? Function on lead development teams providing CMC guidance and strategy including identifying and assessing regulatory risks. ? Ensure the timely preparation, review and submission of CMC documents to regulatory authorities including FDA, EMA and other national authorities, to support the conduct of clinical trials and marketing applications. ? Ensure the compliance of CMC activities with applicable regulatory requirements. ? Evaluate manufacturing processes and changes, assess regulatory implications and support process implementation. ? Assist NIH with inspections and onsite visits with contract organizations. ? Maintain current knowledge of the relevant guidelines and regulations and determine applicability to activities. ? Provide expertise in dose form selection. ? Provide expertise in API development and related activities. 2. Process Chemistry Consultants will support the process chemistry efforts of preclinical and clinical programs of the small molecules in development. Consultants may be asked to provide guidance on process endpoints, recommend assays and milestones to be incorporated into a testing funnel or development plan, and interpret data delivered by research service contractors. The role of the Process Chemistry consultant may include the following responsibilities and others as assigned: may include but are not limited to the following responsibilities and tasks: ? In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage process chemistry to support development of efficient and scalable manufacturing processes, process scale up and implementation of innovative technologies, in support of IND enabling and clinical studies. ? Serve as the process chemistry expert in order to identify potential developmental challenges and suggest strategies to address these challenges on realistic timelines. ? Lead the chemical development activities including scale-up and process development from pilot-scale to commercial scale and technology transfer to commercial plants. ? Manage the process development technology transfer of projects at contract manufacturing sites. ? Oversee the writing of protocols for the manufacture of scale-up batches and associated process development reports. ? Lead the process chemistry activities for compounds in development in accordance with the US regulatory and the ICH guidelines. ? Evaluate manufacturing processes and changes, assessment of regulatory implications and supporting their implementation. ? Maintain current knowledge of the relevant guidelines and regulations. 3. Medicinal Chemistry Medicinal chemistry consultants will be expected to provide senior-level medicinal chemistry expertise and contribute feedback and guidance on projects to the NIH and to LDT members through conference calls and by email. Chemistry consultants will be expected to offer input on project milestones, target product profiles, and testing funnels; provide feedback on chemical structures proposed by a chemistry service contractor for each round of SAR; and evaluate SAR data on a weekly or biweekly basis. A medicinal chemistry consultant may be asked to evaluate the potential tractability (including surrounding IP space) of a chemical structure for medicinal chemistry. Specific consulting responsibilities will depend on the expertise of the individual consultant and the needs of individual projects. The role of the medicinal chemistry consultant may include but is not limited to the following responsibilities and tasks: ? In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage medicinal chemistry programs to facilitate exploratory chemistry, hit-to-lead, lead optimization, IND enabling, and clinical studies. ? Serve as the medicinal chemistry expert in order to identify potential drug discovery and development challenges and suggest strategies to address these challenges. ? Collaborate on design of investigative studies in support of NIH drug discovery and development projects. 4. Regulatory Affairs Regulatory affairs consultants will provide leadership in support of the regulatory affairs strategies of preclinical and clinical programs of the small molecules in development. Consultants may be asked to provide guidance on IND enabling studies and programs to ensure quality and timeliness of regulatory submissions. Consultants will coordinate, prepare, edit and submit applications to regulatory authorities. Consultants will serve as the principal regulatory contact with NIH staff, PIs, and regulatory agencies, as a primary regulatory representative to the FDA. The role of the regulatory affairs consultant may include but is not limited to the following responsibilities and tasks: ? Work within project teams to develop regulatory strategies, identify regulatory risks, and enable timely approval. ? Coordinate the preparation of drafts, editing, review, and submission of regulatory dossiers in support of investigational and new drug applications for US (e.g., IND, Drug Master Files, Technical Files, Annual Reports, Amendments, Supplements, and etc.). ? Ensure that submissions meet format and content requirements applicable to specific US health authority regulatory requirements. ? Provide input on and review specifications, methods, SOPs, protocols, reports, labeling, etc. for regulatory compliance. ? Manage timelines for regulatory submissions. ? Work independently to complete assigned projects. ? Work effectively to coordinate the activities of CROs and consultants in the preparation of regulatory submissions as necessary. ? Advise NIH staff and project teams on issues related to regulatory strategy; identify areas of concern in regards to developing regulations. ? Facilitate consistency in regulatory strategies and documentation by critically reviewing CMC documentation, participating in Reg CMC challenge meetings and integrating regulatory trends and experiences. 5. Bioactivity Assay Development Consultants may be required to evaluate bioactivity assays and recommend strategies and experiments to optimize and/or validate the assays for use in a medicinal chemistry campaign. Assay development consultants may be asked to assist in the establishment of milestones related to assay optimization or validation. The NIH may seek guidance from consultants on the design and interpretation of commonly used in vivo assays, such as cognitive and behavioral tests. Assay-related consultation services may be required on an ad hoc basis or on LDTs. The role of the assay consultant may include but are not limited to the following responsibilities and tasks: ? In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage programs to facilitate lead optimization, IND enabling, and clinical studies. ? Serve as a resource to lead development team members for assay requirements, and logistics to conduct drug development activities for small molecule compounds from the preclinical stage through to the initial clinical stage ? Serve as the assay expert in order to identify potential developmental challenges and suggest strategies to address these challenges. ? Collaborate on design of investigative studies in support of development compounds. 6. Toxicology Consultants may be asked to help establish toxicology endpoints and milestones for a project, recommend assays to be incorporated into a testing funnel or development plan, design toxicology and pharmacology studies, and interpret data delivered by research service contractors. The role of the toxicology consultant may include but is not limited to the following responsibilities and tasks: ? In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage toxicology programs to facilitate lead optimization, IND enabling, and clinical studies. ? Serve as a resource to lead development team members for the toxicology requirements, pharmacology, and logistics to conduct drug development activities for small molecule compounds from the preclinical stage through to the initial clinical stage ? Serve as the toxicology expert in order to identify potential developmental challenges and suggest strategies to address these challenges. ? Collaborate on design of investigative toxicology studies in support of development compounds. ? Review toxicology sections of regulatory filings provided by CROs or PIs. 7. Drug Metabolism and Pharmacokinetics The role of the Drug Metabolism and Pharmacokinetics consultant may include but is not limited to the following responsibilities and tasks: ? In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage PK programs to facilitate assay development, exploratory chemistry, lead optimization, formulation activities, IND enabling, and clinical studies. ? Serve as the PK expert in order to identify potential drug discovery and development challenges such as lead identification and lead development and suggest strategies to address these challenges. ? Collaborate on design of investigative PK studies, PK/PD strategy, experimental design, data analysis and interpretation for discovery and translational projects in support of NIH drug discovery and development projects. 8. Phase I Clinical Consultant The role of the Phase I Clinical consultant may include but is not limited to the following responsibilities and tasks: ? Assist NIH staff in design of Phase I studies to support ongoing projects. Advise on outsourcing specifications for contractors. ? In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, upcoming trials to facilitate clinical studies. ? Serve as the Clinical expert in order to identify potential development and clinical challenges and suggest strategies to address these challenges. QUALIFICATIONS General Experience Consultants must have extensive experience in managing or being a senior leader in drug discovery projects in the biopharmaceutical industry. Experience with drug discovery for nervous system conditions is preferred. Consultants must be able to work in a cross-functional team environment and manage competing priorities. Consultants must have strong interpersonal skills, an attention to detail, excellent organizational, writing, communication, presentation, and documentation skills as well as computer and software literacy. Consultants must have knowledge and understanding of global regulatory regulations and guidelines. Consultants must have experience working with multi-disciplinary teams at a senior level in the biopharmaceutical industry, especially teams with members from outside organizations and members at various management levels. Experiences in team leadership, consulting, or service on strategic and advisory boards will be considered. Specific Discipline Experience The following educational and experience requirements are the minimum acceptable requirements. 1. Chemical Manufacturing and Controls (CMC/Pharmaceutics) Chemical Manufacturing and Controls (CMC/Pharmaceutics) consultants should demonstrate expertise as follows: ? An advanced degree in a science, chemistry degree preferred ? At least 10 years of CMC experience; small molecule experience required ? Previous experience in the preparation and submission of the CMC components of IND/CTA/NDA/MAAs 2. Process Chemistry Process Chemistry consultants should demonstrate expertise as follows: ? An advanced degree in a science is required, chemistry degree preferred. ? 15 years of process and chemical development experience; small molecule experience is required. ? Previous experience in the preparation and submission of the CMC components of IND, CTA, NDA, and MAAs 3. Medicinal Chemistry Medicinal Chemistry consultants should demonstrate high-level expertise as follows: ? An advanced degree in a physical science discipline is required. ? 15 years of medicinal chemistry experience ? Experience in executing and managing drug development tasks, particularly for nervous system conditions. ? A track record of advancing projects into drug development. Measures of success include patents, Investigational New Drug (IND) applications, publications, and drugs brought to market. ? Previous experiences in identifying and anticipating problems early in a project, overcoming technical difficulties, and making strategic decisions that make wise use of limited resources (including terminating projects that appear unlikely to succeed) will be considered as signs of a strong track record in drug development. ? Expertise leading chemistry efforts performed by contract research organizations, and managing drug project portfolios 4. Regulatory Affairs Regulatory affairs consultants should demonstrate high-level expertise as follows: ? An advanced degree in a scientific discipline is required. ? 10 years? experience in the pharmaceutical or other related industry is required. ? 7 years hands-on Regulatory Affairs experience in the pharmaceutical industry dealing with combination products and/or medical devices. ? A good understanding of chemistry, analytics and pharmaceutical technology and in-depth understanding of the drug development process. ? Proven track record of early recognition of potential Regulatory issues especially with IND filings, distilling complex situations, sound risk assessment and overcoming hurdles. ? Experience in the small molecule neurotherapeutic area is required. ? Experience overseeing drafting IND applications for outside organizations is preferred. 5. Bioactivity Assay Development Bioactivity Assay consultants should demonstrate high-level expertise as follows: ? An advanced degree in a scientific discipline is required. ? Application of assays in industrial pharmaceutical discovery and development. ? Application of automated technologies and robotics relevant to pharmaceutical assays. ? Application of a diverse range of cellular techniques in pharmaceutical assays. ? Self-organization, self-direction, critical thinking, and analysis skills. Experience working with multi-disciplinary development teams at a senior level in 6. Toxicology Toxicology consultants should demonstrate high-level expertise in the following: ? An advanced degree in a scientific discipline is required. ? Pharmaceutical toxicology or pharmacology; current DABT Board certification preferred; small molecule and CNS experience preferred. ? Current regulatory drug development process for toxicology. ? Creative and effective resolutions to issues of predictive toxicology. ? Self-organization, self-direction, critical thinking, and analysis skills. 7. Drug Metabolism and Pharmacokinetics Drug Metabolism and Pharmacokinetics consultants should demonstrate high-level expertise as follows: ? An advanced degree in a scientific discipline is required. ? Experience in pharmacokinetics and drug metabolism of small molecules; CNS experience preferred, ? Self-organization, self-direction, critical thinking, and analysis skills. 8. Phase I Clinical Consultant Phase I Clinical consultants should demonstrate high-level expertise as follows: ? An advanced degree in a scientific discipline is required (MD or PhD). ? 10 years? experience in the pharmaceutical or other related industry with responsibility for early clinical trials is required. ? 7 years hands-on Ph I clinical experience in the pharmaceutical industry dealing both in-house and outsourced trials. ? A good understanding of the drug development process. ? Proven track record of early recognition of potential Regulatory issues especially with IND filings, distilling complex situations, sound risk assessment and overcoming hurdles. ? Experience in the small molecule area is required. ? Experience overseeing drafting clinical protocols for outside organizations is preferred. Level of Effort The NIH estimates that it will require the following labor hours and number of consultants for each of the specific disciplines as follows: 1. Chemical Manufacturing and Controls (CMC/Pharmaceutics) Year 1: Up to 800 hours Year 2: Up to 800 hours Year 3: Up to 800 hours Year 4: Up to 800 hours Year 5: Up to 800 hours 2. Process Chemistry Year 1: Up to 800 hours Year 2: Up to 800 hours Year 3: Up to 800 hours Year 4: Up to 800 hours Year 5: Up to 800 hours 3. Medicinal Chemistry Year 1: Up to 600 hours Year 2: Up to 600 hours Year 3: Up to 600 hours Year 4: Up to 600 hours 4. Regulatory Affairs Year 1: Up to 2000 hours Year 2: Up to 2000 hours Year 3: Up to 2000 hours Year 4: Up to 2000 hours Year 5: Up to 2000 hours 5. Bioactivity Assay Development Year 1: Up to 800 hours Year 2: Up to 800 hours Year 3: Up to 800 hours Year 4: Up to 800 hours Year 5: Up to 800 hours 6. Toxicology Year 1: Up to 800 hours Year 2: Up to 800 hours Year 3: Up to 800 hours Year 4: Up to 800 hours Year 5: Up to 800 hours 7. Drug Metabolism and Pharmacokinetics Year 1: Up to 1200 hours Year 2: Up to 1200 hours Year 3: Up to 1200 hours Year 4: Up to 1200 hours Year 5: Up to 1200 hours 8. Phase I Clinical Consultant Year 1: Up to 800 hours Year 2: Up to 800 hours Year 3: Up to 800 hours Year 4: Up to 800 hours Year 5: Up to 800 hours Period of Performance Base Year - September 1, 2014 through August 31, 2015 Option Period One - September 1, 2015 through August 31, 2016 Option Period Two - September 1, 2016 through August 31, 2017 Option Period Three - September 1, 2017 through August 31, 2018 Option Period Four - September 1, 2018 through August 31, 2019 Travel Consultants may be asked to travel for one-day site visits for the launch of each project and for steering committee meetings for the Blueprint Neurotherapeutics Network. The consultant shall make his/her own travel arrangements. The COR shall assist the consultant in identifying a hotel at an acceptable rate, if an overnight stay is required. The Government shall reimburse all reasonable travel costs. Airplane tickets must be purchased from a US carrier, at the coach/economy rate. The Government shall reimburse hotel costs for up to two nights per site visit, as well as food and incidental expenses. The consultant shall make a good faith effort to select travel options that are the most time and cost-effective, given the available options. The consultant shall make a good faith effort to keep food and incidental costs within the typical government per diem rate for the region. The consultant may bill up to 50% of travel hours to the Government, at the negotiated consulting rate. Intellectual Property Consultants who contribute to the creation of new intellectual property will be named as inventors according to US or prevailing patent law. Accordingly, consultants must complete negotiations with the principal investigator?s institution regarding assignment of rights and royalties distribution prior to advising on any activities. The consultant shall provide copies of all intellectual property agreements to the NIH COR, for documentation purposes. Confidential Treatment of Sensitive Information The Contractor shall guarantee strict confidentiality of the information/data that it is provided by the Government or by persons or entities applying to or accepted to the Blueprint Neurotherapeutics Network during the performance of the contract. The Government has determined that the information/data that the Contractor will be provided during the performance of the contract is of a sensitive nature. Disclosure of the information/data, in whole or in part, by the Contractor can only be made after the Contractor receives prior written approval from the Contracting Officer. Whenever the Contractor is uncertain with regard to the proper handling of information/data under the contract, the Contractor shall obtain a written determination from the Contracting Officer. Contractor agrees that it will not use the Confidential Information for any purpose except as set forth within this SOW, unless such time as such Confidential Information becomes public information through the efforts of participants in the Blueprint Neurotherapeutics Network. IT Security Requirements Please refer to Appendix A for IT security requirements. The NIH anticipates awarding multiple consulting contracts under this solicitation.